Cytochrome P-450 plays key roles in the metabolism, activation and detoxification of drugs, endogenous steroids, xenobiotics and environmental carcinogens. Cytochrome P-450 isolated from the liver of rats treated with phenobarbital (PB-P-450) is distinct from the cytochrome P-450 isolated from the liver of rats treated with 3-methylcholanthrene (MC-P-450). Six monoclonal antibodies (MABs) to PB-P-450 and 12 to MC-P-450 were obtained from hybrids made by the fusion of myeloma cells with spleen cells derived from mice immunized with PB- or MC-P-450. These MABs are specific for their respective antigens by radioimmunoassay and double immunodiffusion assays and in inhibition of enzyme activity. These MABs have proved to be useful for identification of specific forms of cytochrome P-450 among the multiple forms present in rat microsomes and for investigation of individual differences in susceptibility to chemical carcinogens.